Xanthoceraside rescues learning and memory deficits through attenuating beta-amyloid deposition and tau hyperphosphorylation in APP mice

Neurosci Lett. 2014 Jun 24:573:58-63. doi: 10.1016/j.neulet.2014.04.032. Epub 2014 May 5.

Abstract

Xanthoceraside, a triterpenoid saponin, has been shown to reverse cognitive deficits in several Alzheimer's disease (AD) animal models. However, the effects of xanthoceraside on the Aβ deposition pathology and the APP processing in AD are unclear. Here, we show that xanthoceraside at doses of 0.08 and 0.32 mg/kg/d for 6 months significantly improved learning and memory impairment in APP transgenic mice assessed by the Y maze and novel object recognition tests. Immunohistochemical analyses revealed that xanthoceraside strongly attenuated β-amyloid deposition in the brains of APP transgenic mice. Western blotting revealed that xanthoceraside decreased tau phosphorylation protein levels at Ser396 and Ser404 in the hippocampus; xanthoceraside also decreased APP protein levels and GSK-3β phosphorylation. These results suggest that xanthoceraside could be a promising novel candidate for the therapy of AD.

Keywords: Amyloid precursor protein; Aβ; Glycogen synthase kinase 3β; Hyperphosphorylated tau; Xanthoceraside.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics*
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Exploratory Behavior / drug effects
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Learning Disabilities / drug therapy
  • Learning Disabilities / metabolism*
  • Learning Disabilities / pathology
  • Maze Learning / drug effects
  • Memory Disorders / drug therapy
  • Memory Disorders / metabolism*
  • Memory Disorders / pathology
  • Mice, Transgenic
  • Phosphorylation
  • Recognition, Psychology / drug effects
  • Saponins / pharmacology*
  • Saponins / therapeutic use
  • Triterpenes / pharmacology*
  • Triterpenes / therapeutic use
  • tau Proteins / metabolism*

Substances

  • APP protein, human
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Saponins
  • Triterpenes
  • tau Proteins
  • xanthoceraside
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3